Learning Objective

Upon completion of this educational activity, participants should be able to:

Identify psychiatric comorbidities that are frequently associated with ADHD and describe an approach to management

Introduction

ADHD is a disorder characterized by frequent and sometimes severe levels of inattention, impulsivity, and hyperactivity.(1-4) Traditionally, it was regarded as a neurodevelopmental condition that emerged during childhood and usually resolved by young adulthood.(3,5) However, subsequent investigations employing genetic approaches and long-term follow-up of children with ADHD have shown that the condition often persists well into adulthood, and continues to exert a pervasive negative impact across multiple life domains.(3,6,7) Indeed, a wide body of evidence has demonstrated a strong link between adult ADHD and poor outcomes related to social function, education, criminality, alcohol use, substance use/abuse, and occupational status.(8,9)

Over the past several years, there has been growing recognition of the frequent association between ADHD and comorbid psychiatric disorders in adult patients. Many of these disorders are identifiable relatively early on in life in the pivotal Multi-Modal Treatment Study of ADHD. Investigators found that nearly 30% of the children with ADHD evaluated exhibited oppositional defiant disorder and/or conduct disorder, 14% had anxiety or depression, and 25% had all three disorders. In fact, only approximately one-third of the children in the study were found to have ADHD alone.

For many 18-22 year old patients with ADHD, the presence of psychiatric comorbidities appears persistent throughout the lifespan. In a large-scale, multisite longitudinal study of college-aged men (n=214) and women (n=229), comprehensive multimethod evaluation combined with expert panel review revealed higher rates of overall comorbidity among college students with well-defined ADHD.(10) Specifically, the results indicated that 55.0% had ≥1 comorbid diagnosis and 31.8% had ≥2, relative to peers without ADHD (11.2% and 4.0%, respectively).(10) Further evaluation revealed the differences in comorbidity rates to be largely attributable to the increased presence of depressive and anxiety disorders, particularly major depressive disorder (active or in partial remission) and generalized anxiety disorder.(10)

Likewise, other studies have reported similar trends among broader populations of adults with ADHD. A national survey published in 2006 found that among adult respondents with ADHD, 47.1% had an anxiety disorder, 38.3% had a mood disorder, and 15.2% had a substance abuse disorder vs 19.5%, 11.1%, and 5.6%, respectively, among respondents without ADHD. Similarly, a separate investigation also found a high prevalence of depression in adults with ADHD compared with non-ADHD controls (14.0% vs 3.2%; P≤.0001). The next 2 most commonly observed psychiatric comorbidities in patients with ADHD, anxiety and bipolar disorder, were observed 3 to 6 times more frequently than in patients without ADHD (P≤.0001). Although less well-characterized in the context of ADHD, personality disorders such as antisocial and borderline personality disorder have also been found to be more frequently expressed in ADHD patients.(11)

In addition, ADHD has also been found to be a significant risk factor for substance use disorder (SUD) among adult patients. A recent exploration of this relationship among twins (N=18,167; 20-45 years of age) found that ADHD symptoms were significantly associated with an increased risk for all SUD types reported (ie, alcohol, illicit drugs, and nicotine).(12) Odds ratios ranged between 1.33 for regular nicotine (95% confidence interval [CI]=[1.12, 1.59]); 2.54 for multiple drug use (95% CI=[2.00, 3.23]), and 3.58 for alcohol dependence (95% CI=[2.86, 4.49]).(12) Additionally, evidence also indicates that ADHD contributes to a faster progression from initial substance use to abuse, and a more aggressive course of abuse.(13)

Psychiatric Comorbidities in Adults with ADHD: Implications for Diagnosis

The frequent presence of psychiatric comorbidities has important implications for the evaluation of adult patients suspected of having ADHD. Manifestations of ADHD tend to be less obvious in adults than in children, often making it difficult to recognize ADHD-specific symptoms against a backdrop of those related to co-occurring conditions. Conversely, symptoms of ADHD can also mask symptoms of other psychiatric disorders. As part of a patient evaluation, establishing the presence of symptoms during childhood may be helpful in distinguishing ADHD from other possible causes of inattention, with the absence of a lifelong pattern prompting consideration of other diagnoses.(4) Risk factor evaluation, likewise, may help inform the diagnosis. However, frequently co-occurring conditions (eg, depression) often share common environmental risk factors with ADHD, and thus may have only limited value in differentiating between different conditions.(14) Many of the psychiatric disorders that are commonly associated with ADHD share similar features and can therefore significantly obscure the diagnostic process (Table 1).

Table 1. Overlapping Symptoms of ADHD and Other Psychiatric Disorders15,16

One, in particular, that has been the subject of increased attention in the context of ADHD is anxiety disorder.(17,18) Indeed, a significant symptom overlap between the two conditions has been consistently observed. Among the symptoms common to both that may complicate diagnosis are restlessness/psychomotor agitation, concentration difficulties, decreased attention, increased distractibility, mood swings, and anger outbursts.(19) In a recent attempt to gain further insight into the implications of this symptom overlap, an investigation into the validity of two widely used ADHD and anxiety rating scales, the Conners Adult ADHD Rating Scale (CAARS) and State Trait Anxiety Inventory scales (STAI), was conducted. The authors of the study found that the CAARS and STAI had limited sensitivity and specificity in patients with comorbid ADHD and anxiety, and concluded that their application may be inadequate to differentially diagnose patients affected by both conditions. Based on their findings, the authors go on to propose that modifications to the two scales might be made to improve their sensitivity and specificity. However, further investigations will be required to determine the diagnostic impact of such modifications.

Like anxiety, bipolar disorder also shares significant symptom overlap with ADHD in adults. Indeed, several studies have noted that symptoms of ADHD are often mistakenly assumed to be part of bipolar disorder in individuals who are affected by both conditions.(20) Overlapping symptoms include distractibility, impulsivity, increased talkativeness, increased motor activity, physical restlessness, and deficiency in expected degree of social inhibitions.(21) However, symptoms reflective of mood dysregulation in bipolar disorder are more likely to be episodic and cyclic in nature.(21) Because comorbid ADHD and bipolar disorder presentation is generally associated with a greater severity of mood disorder symptoms, a more severe disease course, and lower functional scores, failing to render an accurate and complete diagnosis can have an exponential negative impact on patient outcomes over the long-term.(22)

Treatment of Adults with ADHD and Comorbid Psychiatric Conditions

Recognition of comorbid conditions among patients with ADHD is crucial for informing subsequent treatment decisions. An important question that arises in the selection of an appropriate treatment regimen relates to whether treatment efficacy is adversely influenced by the presence of comorbidity. In a review of controlled clinical trials evaluating a range of psychiatric comorbidities (including bipolar disorder, major depressive disorder, oppositional defiant disorder, conduct disorder, and SUD) and its impact on treatment efficacy in adults with ADHD, it was determined that the presence of comorbidity does not substantially alter the safety and efficacy of ADHD pharmacotherapies.(23) Furthermore, the results of the review suggested that treatment of ADHD may actually improve symptoms of the comorbid disorder in conjunction with those of ADHD.(23)

At the same time, it is also important to bear in mind that the choice of therapy requires consideration of the specific type of comorbidity. For example, formulations or specific agents associated with a lower risk of abuse should be prioritized when choosing a treatment for patients demonstrating comorbid drug abuse or who might be suspected of trying to simulate or exaggerate ADHD symptoms in order to obtain stimulants for diversion or abuse.(24) Although methylphenidate (MPH) is currently considered a first-choice medication for symptoms of ADHD, its use with comorbid SUD has historically been challenging due to the potential for abuse of the treatment and because of the possible impact on SUD. Choosing a sustained-release rather than immediate-release formulation, may be one strategy for addressing these concerns, as the subjective effects of MPH are highly dependent on pharmacokinetics.(25) As a general approach, it is recommended that the response to treatment in adults with comorbid ADHD and SUD should be closely observed, with individualized consideration of side effects.(25) As an alternative to MPH, a nonstimulant may be selected. In a 3-month, double-blind, placebo-controlled study of atomoxetine in adults with ADHD and comorbid alcohol use disorder, subjects demonstrated clinically significant improvements in symptoms of ADHD. (Although brief abstinence from alcohol were also observed in the study, the effects on drinking behavior were inconsistent.) For patients with ADHD and bipolar disorder who are at risk for mood destabilization, atomoxetine may also be an appropriate choice, being associated with only a modestly increased risk of manic/hypomanic switches when utilized in combination with mood stabilizers.(24)

In addition to tailoring pharmacologic treatment to accommodate the presence of comorbidities, a multimodal approach that includes cognitive interventions is also recommended. There is general agreement that a multimodal approach is likely to be most effective for the management of ADHD alone, and in recent work, this has been shown to also be true, in the context of ADHD management in the presence of comorbid conditions, with differential but positive effects of a cognitive intervention being observed over time for ADHD symptoms and comorbid problems.(26,27)

Summary

The diagnosis and management of ADHD in adult patients is highly challenging because of the frequent comorbidity of other psychiatric disorders, many of which share overlapping symptoms with those of ADHD. In addition to creating diagnostic challenges, the presence of psychiatric comorbidities also has the potential to significantly influence treatment outcomes. As a result, it is of critical importance that healthcare providers involved in the care of adult patients with ADHD (confirmed or suspected) maintain awareness of commonly occurring psychiatric comorbidities and familiarity with symptom overlap patterns in order to render an accurate and complete diagnosis. This, in turn, will enable them to make appropriate recommendations for treatment and ultimately improved patient health outcomes over the long-term.

Clinical Pearls

In addition to applying current guideline criteria for the diagnosis of ADHD in adult patients, clinicians should also perform a thorough evaluation to detect the presence of any psychiatric comorbidities

To optimize ADHD management and overall patient outcomes, clinicians should provide pharmacologic and nonpharmacologic intervention that addresses not only ADHD but also any psychiatric comorbidities

Youngstrom EA, Arnold LE, Frazier TW. Bipolar and ADHD Comorbidity: Both Artifact and Outgrowth of Shared Mechanisms. Clinical psychology : a publication of the Division of Clinical Psychology of the American Psychological Association. 2010;17(4):350-359.

Duffy A. The nature of the association between childhood ADHD and the development of bipolar disorder: a review of prospective high-risk studies. Am J Psychiatry. 2012;169(12):1247-1255.

Target Audience

This educational initiative has been designed for primary care clinicians involved in the management of adult patients with ADHD.

Directions to Learner

There are no fees for participating and receiving CME credit for this enduring activity. During the period of January 10, 2018 through January 10, 2019, participants must:

Read the learning objective and faculty disclosures

Study the educational activity

Complete the posttest and the evaluation form

A statement of credit will be issued upon receipt of a completed activity evaluation form and a completed posttest with a score of 100%.

Accreditation Statement

Integrity Continuing Education, Inc. is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

For questions regarding the accreditation of this activity, please contact Integrity Continuing Education, Inc.: via email at This email address is being protected from spambots. You need JavaScript enabled to view it.
or by phone at (888) 835-4004.

CREDIT DESIGNATION

Integrity Continuing Education, Inc. designates this enduring activity for a maximum of 0.25 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Disclosure of Conflicts of Interest (COI)

Integrity Continuing Education, Inc. requires instructors, planners, managers and other individuals who are in a position to control the content of this activity to disclose any real or apparent COI they may have as related to the content of this activity. All identified COI are thoroughly vetted by Integrity Continuing Education, Inc. for fair balance, scientific objectivity of studies mentioned in the materials or used as the basis for content, and appropriateness of patient care recommendations.

The following faculty/planners reported their financial relationships or relationships to products or devices they or their spouse/life partner have with commercial interests related to the content of this CME activity:

Patima Tanapat, PhD, has no real or apparent conflicts of interest to disclose.

Disclosure of Unlabeled Use

This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the US Food and Drug Administration. Integrity Continuing Education, Inc. and Shire do not recommend the use of any agent outside of the labeled indications.

The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of Integrity Continuing Education, Inc. or Shire. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.

Disclaimer

The information provided at this CME activity is for continuing education purposes only and is not meant to substitute for the independent medical judgment of a physician relative to diagnostic and treatment options of a specific patient’s medical condition.